Yersinia YopP-induced apoptotic cell death in murine dendritic cells is partially independent from action of caspases and exhibits necrosis-like features |
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Authors: | Sabine Gröbner Stella E Autenrieth Irena Soldanova Dani S J Gunst Martin Schaller Erwin Bohn Steffen Müller Martin Leverkus Sebastian Wesselborg Ingo B Autenrieth Stefan Borgmann |
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Institution: | Institute of Medical Microbiology and Hygiene, Eberhard-Karls-University of Tübingen, Elfriede-Aulhorn-Str. 6, D-72076, Tübingen, Germany. sabine.groebner@med.uni-tuebingen.de |
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Abstract: | Yersinia outer protein P (YopP) is a virulence factor of Yersinia enterocolitica that is injected into the cytosol of host cells where it targets MAP kinase kinases (MKKs) and inhibitor of κB kinase (IKK)-β
resulting in inhibition of cytokine production as well as induction of apoptosis in murine macrophages and dendritic cells
(DC). Here we show that DC death was only partially prevented by the broad spectrum caspase inhibitor zVAD-fmk, indicating
simultaneous caspase-dependent and caspase-independent mechanisms of cell death induction by YopP. Microscopic analyses and
measurement of cell size demonstrated necrosis-like morphology of caspase-independent cell death. Application of zVAD-fmk
prevented cleavage of procaspases and Bid, decrease of the inner transmembrane mitochondrial potential ΔΨm and mitochondrial release of cytochrome c. From these data we conclude that YopP-induced activation of the mitochondrial
death pathway is mediated upstream via caspases. In conclusion, our results suggest that YopP simultaneously induces caspase-dependent
apoptotic and caspase-independent necrosis-like death in DC. However, it has to be resolved if necrosis-like DC death occurs
independently from apoptotic events or as an apoptotic epiphenomenon. |
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Keywords: | Yersinia YopP Apoptosis Necrosis-like Caspase-independent Cell death |
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